Sub-acute cerebellar degeneration with anti-Yo autoantibodies: immunohistochemical analysis of the immune reaction in the central nervous system.
We report the pathological findings of a woman with a sub-acute cerebellar syndrome who had undergone surgery 3 years before for endometrial carcinoma. Both serum and cerebrospinal fluid contained high titres of autoantibodies against the cytoplasm of Purkinje cells that recognized a band of 62 kDa on immunoblotting of neuronal extracted proteins (pattern anti-Yo). No tumour was found despite a full range of gynaecological investigations; the neoplastic marker CA125 was slightly elevated and oligoclonal bands were detected in the cerebrospinal fluid. The patient died from acute myocardial infarction 4 months after developing this syndrome. At autopsy, no macroscopic evidence of tumour was obtained and the brain showed no abnormalities. On microscopic examination of the central nervous system diffuse degeneration of Purkinje cells could be seen throughout the cerebellum. Immunohistochemical analysis showed a CD8 lymphocyte infiltration in the cerebellum and cerebral cortex and diffuse microglial activation throughout the brain. These cells expressed high levels of MHC-II antigens on their cell membranes. The serum autoantibodies reacted with the cytoplasm of the remaining Purkinje cells. The short interval between the onset of symptoms and death of the patient could explain the difference between our findings and those reported in the literature in which no inflammatory infiltrates were detected. The immunohistochemical findings as well as the inflammatory cerebrospinal fluid profile seen in our case seem to support the concept that in paraneoplastic cerebellar degeneration with anti-Yo antibodies, an immune mediated mechanism is responsible for the damage to the cerebellum.
Giometto
B
B
Department of Neurology and Psychiatry (Second Neurological Clinic), University of Padova, Italy.
Marchiori
G C
GC
Nicolao
P
P
Scaravilli
T
T
Lion
A
A
Bardin
P G
PG
Tavolato
B
B
D000368:Aged; D001324:Autoantigens / Q000032:analysis*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes; D002526:Cerebellar Diseases / Q000276:immunology* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000276:immunology*; D017809:Fatal Outcome; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000276:immunology*; D009419:Nerve Tissue Proteins; D011689:Purkinje Cells / Q000737:chemistry / Q000473:pathology
D001324:Autoantigens; C063762:CDR1 protein, human; C095184:CDR2 protein, human; D004268:DNA-Binding Proteins; D006680:HLA Antigens; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins